Diabetes and hyperglycemia impair activation of mitochondrial KATP channels
Diabetes and hyperglycemia impair activation of mitochondrial KATP channels
复制标题
DOI：
10.1152/ajpheart.2001.280.4.h1744
复制
发表时间：
2001-04-01
影响因子：
4.8
通讯作者：
Warltier, DC
中科院分区：
文献类型：
--
作者：
Kersten, JR;Montgomery, MW;Warltier, DC
高血压是糖尿病患者心血管死亡率的重要预测因子。我们研究了糖尿病或急性高血糖减弱由线粒体ATP调节的钾（K-ATP）通道激活引起的心肌梗死面积减少的假设。急性仪器巴比妥麻醉犬进行60分钟的冠状动脉闭塞和3小时的再灌注。对照犬、糖尿病犬（链脲佐菌素-四氧嘧啶治疗后3周）和高血糖犬（静脉注射15%葡萄糖）的心肌梗死面积（氯化三苯四氮唑染色）分别为梗死风险面积（AAR）的25 +/- 1、28 +/- 3和25 +/- 1%。二氮嗪（2.5 mg/kg iv）显著减少梗死面积（10 +/-1%AAR，P< 0.05），但在糖尿病（28 +/- 5%）或中度高血糖（血糖310 +/- 10 mg/dl; 23 +/- 2%）的情况下不产生保护作用。二氮嗪的剂量与高血糖程度呈交互作用。重度（血糖574 +/- 23 mg/dl）但非中度高血糖阻断了高剂量（5.0 mg/kg）二氮嗪的作用[分别为26 +/- 3、15 +/- 3（P< 0.05）和11 +/- 2%（P< 0.05）]。两组之间的全身血流动力学、AAR或冠状动脉侧支血流（通过放射性微球）无差异。结果表明，糖尿病或高血糖损害线粒体K-ATP通道的激活。
Hyperglycemia is an important predictor of cardiovascular mortality in patients with diabetes. We investigated the hypothesis that diabetes or acute hyperglycemia attenuates the reduction of myocardial infarct size produced by activation of mitochondrial ATP-regulated potassium (K-ATP) channels. Acutely instrumented barbiturate-anesthetized dogs were subjected to a 60-min period of coronary artery occlusion and 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium chloride staining) was 25 +/- 1, 28 +/- 3, and 25 +/- 1% of the area at risk (AAR) for infarction in control, diabetic (3 wk after streptozotocin-alloxan), and hyperglycemic (15% intravenous dextrose) dogs, respectively. Diazoxide (2.5 mg/kg iv) significantly decreased infarct size (10 +/- 1% of AAR, P< 0.05) but did not produce protection in the presence of diabetes (28 +/- 5%) or moderate hyperglycemia (blood glucose 310 +/- 10 mg/dl; 23 +/- 2%). The dose of diazoxide and the degree of hyperglycemia were interactive. Profound (blood glucose 574 +/- 23 mg/dl) but not moderate hyperglycemia blocked the effects of high-dose (5.0 mg/kg) diazoxide [26 +/- 3, 15 +/- 3 (P< 0.05), and 11 +/- 2% (P< 0.05), respectively]. There were no differences in systemic hemodynamics, AAR, or coronary collateral blood flow (by radioactive microspheres) between groups. The results indicate that diabetes or hyperglycemia impairs activation of mitochondrial K-ATP channels.